System and method for predicting an excitation pattern of a deep brain stimulation

ABSTRACT

A system and method for analyzing bioelectrical signals generated during a deep brain stimulation (DBS) includes an apparatus having a housing having a signal input and a signal output and an electrical circuit disposed within the housing and electrically coupled between the signal input and the signal output. The electrical circuit is configured to receive bioelectrical signals corresponding to a cyclic excitation signal transmitted by a pulse generator during a DBS and generate an output signal comprising a series of timing pulses, wherein each timing pulse simulates an envelope of the cyclic excitation signal. The signal output of the housing is electrically coupleable to an auxiliary trigger input of an imaging system and the series of timing pulses can be used to trigger image data acquisition.

BACKGROUND OF THE INVENTION

Embodiments of the invention relate generally to a system and method forsynchronizing image data acquisition with a deep brain stimulation, andmore particularly to a system and method that generates a timing pulsefor triggering image data acquisition from bioelectrical data acquiredduring short term cycling of a deep brain stimulation.

Deep brain stimulation (DBS) is used for treating disabling neurologicalsymptoms and psychiatric disorders. The procedure uses a neurostimulatorto deliver electrical stimulation to the brain by way of surgicallyimplanted electrodes. Depending on the condition being treated, theelectrodes can be used to target certain cells and chemicals within thebrain or can be targeted toward areas of the brain that control movementor regulate abnormal impulses. In this later case, the electricalstimulation can be used to disrupt abnormal nerve signals that causetremor and other neurological symptoms. Over the past 20 years, morethan 100,000 Parkinson's disease, essential tremor, dystonia andobsessive-compulsive disorder patients have seen significant symptomrelief due to DBS treatment. Evidence now accumulates indicating thatpatients with chronic pain, post-traumatic stress disorder, and obesitymay also benefit from DBS treatments.

Despite the long history of DBS, its underlying principles andmechanisms are still not clear. In particular, the understanding of howthe brain responds to different DBS excitation parameters, such aselectrode choice, frequency, current/voltage and pulsewidth is limited.There is no real time feedback mechanism to let a clinician decidewhether DBS has its intended effect or whether the stimulationparameters are optimal for each individual patient. The only currentoption is to watch the patient evolve over a signification period oftime, often months, and determine thereafter if symptoms improve.Feedback in the form of qualitative or quantitative measurements ofbrain response to DBS may aid in optimizing the DBS excitationparameters for treating conditions such as dystonia or depression.

Functional magnetic resonance imaging (fMRI) is one of the fewnon-invasive tools that could be used for such feedback. In particular,fMRI might be used to provide a quick and efficient feedback mechanismby highlighting areas of brain activity related to DBS stimulation andallowing optimization of DBS stimulation parameters in close to realtime. However, fMRI is currently not easily achievable in patients withimplanted DBS pulse generators due to the longstanding FDA restrictionthat prohibits patients with implanted DBS pulse generators fromundergoing MRI

Recent label changes for Medtronic® DBS hardware permit patients withinternalized pulse generator hardware to undergo MRI during active DBS.While DBS electrodes can be cycled ON and OFF during a given DBS, thereis no way to know whether the DBS excitation cycle is in the ON or OFFcondition when the patient is inside the MRI scanner because theprogramming of the DBS device can only be done outside the MRI scanner.Even if the parameters of the DBS were known prior to fMRI acquisition,a multi-second time lag occurs during which the stimulation parametersare communicated from the controller to the pulse generator andthereafter from the pulse generator to the electrodes resulting indifferences between the requested and measured stimulation periods. Thiscommunication time lag and the long time interval between the pulsegenerator programming and actual fMRI onset can lead to large errors inassessing the stimulation state, which can cause significant drops infMRI sensitivity. Consequently, fMRI imaging data cannot be properlybinned corresponding to ON and OFF conditions of the DBS excitationcycle.

It would therefore be desirable to have a system and method capable ofaccurately detecting the timing of the excitation pattern of a DBS andpredicting a future timing pattern of the excitation pattern. It wouldalso be desirable for such a system and method to generate an outputfrom the future timing pattern in the form of a time stamp log to permitmedical images acquired during DBS excitation to be binned in a mannercorresponding to the DBS excitation. It would also be desirable for sucha system and method to enable medical data acquisition to besynchronized with the ON and OFF conditions of a DBS excitation cyclesuch that brain regions activated as a consequence of the DBS may beidentified in the acquired medical data. It would further be desirableto produce an output representative of the DBS excitation pattern tofacilitate analysis of the health of the DBS system.

BRIEF DESCRIPTION OF THE INVENTION

In accordance with one aspect of the invention, an apparatus foranalyzing bioelectrical signals generated during a deep brainstimulation (DBS) includes a housing having a signal input and a signaloutput and an electrical circuit disposed within the housing andelectrically coupled between the signal input and the signal output. Theelectrical circuit is configured to receive bioelectrical signalscorresponding to a cyclic excitation signal transmitted by a pulsegenerator during a DBS and generate an output signal comprising a seriesof timing pulses, wherein each timing pulse simulates an envelope of thecyclic excitation signal.

In accordance with another aspect of the invention, a method foranalyzing bioelectrical signals generated during a deep brainstimulation (DBS) includes obtaining bioelectrical signals generatedfrom excitation signals transmitted by a pulse generator during a DBS.The method also includes transforming the bioelectrical signals into aseries of digital logic pulses representing a plurality of activeportions of the DBS, each active portion comprising a plurality ofdigital logic pulses. The method further includes generating a series oftiming pulses from the series of digital logic pulses, each timing pulsesynchronized with predicted timing of an active portion of the DBS.

In accordance with yet another aspect of the invention, a medicalimaging system includes an imaging device configured to acquire medicalimage data from a patient and reconstruct medical images therefrom. Themedical imaging system also includes a sensor system configured todetect bioelectrical signals generated within the patient during a deepbrain stimulation (DBS) and a DBS signal emulator removeably coupleableto a trigger input of the imaging device and to the sensor system. TheDBS signal emulator is programmed to transform bioelectrical signalsreceived from the sensor system into a series of timing pulses havingpulse widths predictive of active periods of the DBS and output theseries of timing pulses to the trigger input of the imaging device.

Various other features and advantages will be made apparent from thefollowing detailed description and the drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

The drawings illustrate embodiments presently contemplated for carryingout the invention.

In the drawings:

FIG. 1 is a schematic block diagram of a deep brain stimulation (DBS)detection system, according to an embodiment of the invention.

FIG. 2 is a schematic diagram of an electrical circuit employed in a DBSwaveform emulator integrated within the DBS detection system of FIG. 1,according to an embodiment of the invention.

FIG. 3 is a schematic block diagram of an exemplary MR imaging systemfor use with an embodiment of the invention.

FIG. 4 is a flowchart illustrating a technique for analyzing the DBSstimulation parameters, according to an embodiment of the invention.

FIG. 5 illustrates raw and filtered waveforms corresponding to anexemplary DBS stimulation.

DETAILED DESCRIPTION

In general, embodiments of the invention described herein are directedto a system and method for detecting the excitation pattern of a deepbrain stimulation (DBS) and converting the detected excitation patterninto a timing pulse that permits image data acquisition to besynchronized with the DBS.

While embodiments of the invention are discussed below in regard tosynchronizing DBS with the acquisition of functional magnetic resonanceimage (fMRI) data, the systems and methods disclosed herein may be usedwith alternative image data acquisition techniques, including positronemission tomography (PET) and optical imaging. The techniques describedherein may also be used in conjunction with electroencephalography (EEG)or magneto-encephalography (MEG) to pick up the functional response of aDBS system with the associated detectors. Still further, the techniquesdescribed herein may be utilized to analyze the health of a DBS systemand determine whether the DBS system is transmitting stimulation signalsin accordance with desired program parameters.

FIG. 1 depicts a deep brain stimulation (DBS) detection system 10according to one embodiment of the invention. The DBS detection system10 includes one or more leads or electrodes 12 surgically implantedwithin the one or more regions of the brain 14 of a patient 16. Eachimplanted electrode 12 is configured to apply stimulation signals to atargeted region of the brain 14. While two electrodes 12 are illustratedin FIG. 1, it will be understood that system 10 may include a singleimplanted electrode as well as three or more electrodes, each of whichmay be positioned and configured to facilitate unipolar or bipolarstimulation.

Each implanted electrode 12 is connected through an extension wire 18that is passed under the skin of the patient 16 to a pulse generator 20configured to deliver stimulation signals to electrodes 12. Pulsegenerator 20 may include a power supply (not shown) such as a battery orother type of power storage device and microelectronic circuitry (notshown) that may include hardware and/or software for generating andoutputting stimulation signals in response to control signals orcommands. In some embodiments, pulse generator 20 may further include astorage unit (not shown) that permits patient-specific data to be storedwithin the pulse generator 20.

In the illustrated embodiment, pulse generator 20 is an internal pulsegenerator that is implanted beneath the skin of the patient 16, such as,for example, under the clavicle as shown in FIG. 1. However, internalpulse generator 20 may be located elsewhere within the patient 16 inalternative embodiments such as, for example, lower in the chest or overthe abdomen. As one non-limiting example, internal pulse generator 20 isan Activa PC Neurostimulator manufactured by Medtronic®. In alternativeembodiments, pulse generator 20 may be an external device coupled toimplanted electrodes 12.

In the case of an implanted pulse generator, the pulse generator 20 isprogrammed with a wireless device 22 that is held over the skin of thepatient 16 proximate the implanted location of the pulse generator 20.The programming defines the excitation parameters of the DBS, which canbe adjusted as the patient's condition changes over time. The circuitrywithin the pulse generator 20 generates pulse sequences in accordancewith the stimulation parameters that send excitation signals toimplanted electrodes 12. The stimulation can be provided in a cyclingfashion and at various currents, voltages, frequencies, and pulse widthsbased on the desired treatment.

A sensor system 24 is provided to sense and track the stimulation signaltransmitted by the internal pulse generator 20 to the implantedelectrodes 12. In one embodiment, sensor system 24 is an arrangement ofthree EKG electrodes 26, 28, 30 that are affixed to the skin surface ofthe patient 16 to measure bioelectrical signals from the patient 16,which include physiological signals generated by the patient's anatomy(e.g., the heart) and voltages generated by the small currents flowingthrough the patient 16 as a consequence of the DBS. In the illustratedembodiment, EKG electrodes 26, 28, 30 are applied to the patient 16proximate the forehead, near the internal pulse generator 20, andabdomen respectively and may be used to sense a DBS excitation patterngenerated by implanted electrodes 12 configured for bipolar and/ormonopolar operation modes. However, a skilled artisan will recognizethat EKG electrodes 26, 28, 30 may be positioned in alternativelocations on the patient 16 such as on the multiple locations on thechest or left arm, right arm, and at a reference location, asnon-limiting examples, in embodiments that utilize electrodes 12configured for monopolar operation. In yet alternative embodiments,sensor system 24 may include sensors provided in the form of loops orplates (not shown) that are configured to pick up the DBS signalsthrough inductive or capacitive coupling to the internal pulse generator20.

A DBS waveform emulator 32 is used in conjunction with the sensor system24 to detect the DBS excitation pattern generated by the internal pulsegenerator 20 and transform the detected signal into a pulse sequencethat emulates the detected pattern. DBS waveform emulator 32 includes ahousing 34 with at least one input port 36 and at least one output port38. A bio-amplifier 40, such as a commercial device, ETH-256,manufactured by iWorx, Dover, N.H. as a non-limiting example, is coupledbetween sensor system 24 and the input port 36 of DBS waveform emulator32 to electrically isolate the patient 16 from the DBS waveform emulator32 and amplify the incoming signal from EKG electrodes 26, 28, 30. In analternative, embodiment bio-amplifier 40 may be integrated within thehousing 34 of DBS waveform emulator 32.

An electrical circuit 42, illustrated in FIG. 2, is provided within thehousing 34 of DBS waveform emulator 32 and coupled between the inputport 36 and output port 38 thereof. As described in more detail below,the electrical circuit 42 is configured to transform bioelectricalsignals received from sensor system 24 into a series of pulses thatrepresent predicted active periods and non-active periods of a cyclicdeep brain stimulation. The electrical circuit 42 includes one or morefilters 44 that eliminate artifacts caused by non-brain sources from theincoming, raw signal received from bio-amplifier 40. In one non-limitingembodiment, filter 44 is a 100 Hz high pass filter configured to removethe heart signal. However, it is contemplated that high pass filter 44may be alternatively configured to remove other undesirable frequencycomponents from the raw signal.

DBS waveform emulator 32 also includes a logic buffer or comparatorcircuit 46 that performs an analog-to-digital signal conversion with anadjustable threshold and separates the actual DBS signal generated byinternal pulse generator 20 from noise. This adjustable threshold may bemanually adjusted using an adjustment dial 48 (FIG. 1) provided on theDBS waveform emulator 32 or, in alternative embodiments, using analgorithm that sets the threshold. In one embodiment comparator circuit46 performs a transistor-transistor logic (TTL) signal conversion.Alternatively, comparator circuit 46 may be configured to output otherdigital logic signals, including CMOS, ICL, or LVDS as non-limitingexamples. A DC-blocking capacitor 50 may be provided between the highpass filter 44 and comparator circuit 46. Alternatively, the DC-blockingfunctionality may be integrated within the high pass filter 44. A pulsestretcher 52 coupled to the output of the comparator circuit 46 ensuresthat a single TTL signal is generated for a single incoming DBS pulse.The resulting output from pulse stretcher 52 is a series of digitallogic pulses that represent active portions of the cyclic DBS excitationpattern, with each active portion of the pattern including a series ofindividual digital logic pulses representative of the multipleexcitation signals delivered during a respective ON portion of an ON/OFFcycle of the DBS excitation.

A microprocessor 54 receives the series of digital logic pulses from thepulse stretcher 52. In one embodiment microprocessor 54 is an ArduinoMicro microprocessor. However, one skilled in the art will recognizethat any suitable microprocessor may be used to carry out the desiredoperations, which include detecting the start and stop times of thepulse cycles and ignoring noise and erroneous signals in the filtereddata. The microprocessor 54 is programmed to record the pulse timing ofthe cyclic DBS excitation pattern in real time and calculate the periodof the cyclic excitation pattern by averaging multiple cycles. Afterrecording the pulse timing, microprocessor 54 generates an output thatemulates the DBS waveform. In one embodiment, the output is in the formof a log of time stamps that predict the start time and duration offuture active transmission periods of neurological excitation. In suchan embodiment the microprocessor 54 may be configured to optionallyinclude a clock (55) 55 (shown in phantom) that records timing of thedigital logic pulses and is used as a reference for the generated timestamp log. Microprocessor 54 may further be configured having anoptional memory 57 (shown in phantom) for storing the generated timestamp log. Alternatively, the time stamp log may output to an auxiliarystorage device, such as, for example, computer 74 or database 76 of FIG.1.

In another embodiment, the output generated by the microprocessor 54 isin the form of a series of timing pulses. The timing pulses of theoutput signal simulate the envelope of the cyclic DBS excitationpattern, with the pulse width of each timing pulse approximating theduration of an active or ON portion of a respective ON/OFF cycle. Themicroprocessor 54 is further programmed to identify a signal lock if thenumber of recorded digital logic pulses exceeds a predeterminedthreshold, as described in more detail below.

Referring again to FIG. 1, in some embodiments DBS waveform emulator 32further includes one or more additional inputs or dials 56, 58 (shown inphantom) that permit an operator to input one or more expectedparameters of the DBS stimulation to the microprocessor 54. In oneembodiment, dial 56 is used to indicate the total expected, programmedperiod of the DBS—that is the sum of the ON and OFF portions of a signalperiod. Dial 58 represents the expected frequency programmed in pulsegenerator 20.

A power switch 60 is provided on the housing 34 for controlling thesupply of power to DBS waveform emulator 32. An optional powerindicating light 62 (shown in phantom) may be provided on the housing 34to identify the ON/OFF status of DBS waveform emulator 32. DBS waveformemulator 32 may further include an operator indicator 64 that signalswhen DBS waveform emulator 32 is locked on the stimulation signalgenerated by pulse generator 20. In the illustrated embodiment, theoperator indicator 64 is provided in the form of a lock light. However,it is contemplated that DBS waveform emulator 32 may be configured toinclude a speaker (not shown) that outputs an audible signal uponacquiring a signal lock. This speaker may further be configured togenerate an audible signal representative of the digital logic signalfrom the pulse stretcher 52, which may be used by the operator inthreshold adjustments. An output light 66 is also provided on housing 34that indicates when DBS waveform emulator 32 is outputting a TTL signalpredictive of the DBS. One or more additional indicator lights 68 (shownin phantom) may optionally be included on housing 34 to indicate thestatus of intermediate processing steps being carried out by theelectrical circuit 42.

DBS waveform emulator 32 further includes a display 70, such as an LCDdisplay for example, that may be configured to report various parametersrelevant to the signal transformation. As non-limiting examples, display70 may include the frequency as the adjustment dial 48 is manipulated,timing of the measured ON and OFF periods of the DBS stimulation, ameasured difference or wander between the actual (measured) timing ofthe ON and OFF periods and the predicted timing of the ON and OFFperiods after signal lock, and/or an elapsed time from signal lock.

Data measured in real time, including the time stamps of the measuredand predicted pulses can be output from the DBS waveform emulator 32 fordisplay on an auxiliary display 72 and/or output to a serial portconnection, which can be read by a computer 74 or other device. Theoutput port 38 of DBS waveform emulator 32 may be also be connected to adatabase 76 for storage and later retrieval of data corresponding to thedetected DBS excitation pattern received from sensor system 24 and thedigital logic pulse or output timing signal 78 generated bymicroprocessor 54. In another embodiment described in additional below,the output port 38 of DBS waveform emulator 32 is coupled to anauxiliary trigger input or input data acquisition board 80 of an imagingdevice 82, such as the auxiliary input 84 of MRI scanner 86 illustratedin FIG. 3 and is used to trigger the start of an image data acquisitionsequence such as, for example, an fMRI scan. While DBS waveform emulator32 is depicted as a standalone device in FIG. 1, it is contemplated thatthe components or the software equivalents thereof can be incorporateddirectly within computer 74 or imaging device 82 in alternativeembodiments.

Referring now to FIG. 3, the major components of a MRI scanner 86useable with the DBS detection system 10 of FIG. 1 are shown accordingto an exemplary embodiment of the invention. The operation of the MMscanner 86 is controlled for certain functions from an operator console88, which in this example includes a keyboard or other input device 90,a control panel 92, and a display screen 94. The operator console 88communicates through a link 96 with a separate computer system 98 thatenables an operator to control the production and display of images onthe display screen 94. The computer system 98 includes a number ofmodules which communicate with each other through a backplane 100. Thesemodules include an image processor module 102, a CPU module 104 and amemory module 106, known in the art as a frame buffer for storing imagedata arrays. The computer system 98 communicates with a separate systemcontrol 108 through a high speed serial link 110. The input device 90can include a mouse, joystick, keyboard, track ball, touch activatedscreen, light wand, voice control, card reader, push-button, or anysimilar or equivalent input device, and may be used for interactivegeometry prescription.

The system control 108 includes a set of modules connected together by abackplane 112. These include a CPU module 114 and a pulse generatormodule 116 which connects to the operator console 88 through a seriallink 118. It is through serial link 118 that the system control 108receives commands from the operator to indicate the scan sequence thatis to be performed. The pulse generator module 116 operates the systemcomponents to carry out the desired scan sequence and produces datawhich indicates the timing, strength and shape of the RF pulsesproduced, and the timing and length of the data acquisition window. Thepulse generator module 116 connects to a set of gradient amplifiers 120,to indicate the timing and shape of the gradient pulses that areproduced during the scan. The pulse generator module 116 can alsoreceive timing data through an auxiliary trigger input 84, which may becoupled to output of the DBS waveform emulator 32 of FIG. 1. Andfinally, the pulse generator module 116 connects to a scan roominterface circuit 122 which receives signals from various sensorsassociated with the condition of the patient and the magnet system. Itis also through the scan room interface circuit 122 that a patientpositioning system 124 receives commands to move the patient to thedesired position for the scan.

The gradient waveforms produced by the pulse generator module 116 areapplied to the gradient amplifier system 120 having Gx, Gy, and Gzamplifiers. Each gradient amplifier excites a corresponding physicalgradient coil in a gradient coil assembly generally designated 126 toproduce the magnetic field gradients used for spatially encodingacquired signals. The gradient coil assembly 126 forms part of aresonance assembly 128 which includes a polarizing magnet 130 and awhole-body RF coil 132. A transceiver module 134 in the system control108 produces pulses which are amplified by an RF amplifier 136 andcoupled to the whole-body RF coil 132 by a transmit/receive switch 138.The resulting signals emitted by the excited nuclei in the patient maybe sensed by the same whole-body RF coil 132 and coupled through thetransmit/receive switch 138 to a preamplifier 140. The amplified MRsignals are demodulated, filtered, and digitized in the receiver sectionof the transceiver module 134. The transmit/receive switch 138 iscontrolled by a signal from the pulse generator module 116 toelectrically connect the RF amplifier 136 to the whole-body RF coil 132during the transmit mode and to connect the preamplifier 140 to thewhole-body RF coil 132 during the receive mode. The transmit/receiveswitch 138 can also enable a separate RF coil (for example, a surfacecoil) to be used in either the transmit or receive mode.

The MR signals picked up by the whole-body RF coil 132 are digitized bythe transceiver module 134 and transferred to a memory module 142 in thesystem control 108. A scan is complete when an array of raw k-space datahas been acquired in the memory module 142. This raw k-space data isrearranged into separate k-space data arrays for each image to bereconstructed, and each of these is input to an array processor 144which operates to Fourier transform the data into an array of imagedata. This image data is conveyed through the serial link 110 to thecomputer system 98 where it is stored in memory. In response to commandsreceived from the operator console 88 or as otherwise directed by thesystem software, this image data may be archived in long term storage orit may be further processed by the image processor module 102 andconveyed to the operator console 88 and presented on the display screen94.

Referring to FIG. 4 in conjunction with the elements of FIGS. 1-3 whereappropriate, a DBS excitation prediction technique 146 is illustratedaccording to an embodiment of the invention. Technique 146 begins atstep 148 by setting pulse generator 20 to generate a cyclic DBSexcitation pattern using programming device 22. This cyclic excitationpattern causes implanted electrodes 12 deliver stimulation pulses duringa set “active” or ON period followed by a set “non-active” periodwherein the implanted electrodes 12 are OFF. In one embodiment, theduration of the ON and OFF periods may be selected based on theresolution of the type of data acquisition being synchronized with theDBS stimulation. For example, in embodiments where the DBS stimulationis used to trigger fMRI acquisition, the DBS stimulation is programmedto set a cyclic ON/OFF pattern where the duration of each ON and OFFperiod is multiple seconds, such as 20 seconds ON and 10 seconds OFF asone non-limiting example. In alternative embodiments where the DBSstimulation is synchronized with data acquisition that occurs atmillisecond resolution, such as EEG, the duration of each ON and OFFperiod may be shortened accordingly.

At step 150, sensor system 24 is coupled to or positioned in closeproximity of the patient 16 in a manner that permits sensor system 24 tosense bioelectrical signals generated within the patient 16 responsiveto a DBS. In one embodiment, bioelectrical sensors 26 are affixed to thepatient 16 while the patient 16 remains outside the MRI scanner 86.Alternatively, the bioelectrical sensors 26 may remain affixed to thepatient 16 when the patient 16 is introduced to the MRI scanner 86.

At step 152, adjustment dial 48 is manipulated until the reportedfrequency of the amplified signal received from sensor system 24corresponds to the frequency DBS signal of the particular patient 16. Inembodiments where DBS waveform emulator 32 includes optional dials 56,58, the operator may also set the total expected, programmed period andthe expected frequency programmed in the pulse generator 20 via dials56, 58 at step 152.

The DBS excitation signal received from sensors 26 is monitored andtransformed into a series of digital logic pulses at step 154 afterpassing through the various circuitry elements of DBS waveform emulator32. As described in detail with respect to FIG. 2, the series of digitallogic pulses represents active or ON portions of the cyclic DBSexcitation, with each active or ON portion including numerous individualdigital logic pulses corresponding to individual electrode triggers.Technique 146 uses accumulated data to measure the timing of the cyclicON/OFF excitation pattern generated from the DBS signal and maintains apulse count for the accumulated data.

The DBS waveform emulator 32 determines whether the pulse count iswithin a predetermined threshold at step 156. This predeterminedthreshold is an integer value that may be programmed on microprocessor54 or selected by an operator prior to an imaging procedure according toalternative embodiments. Once a predetermined number of pulses (within adesired tolerance) are measured 158, microprocessor 54 generates anoutput signal that causes lock light 64 to illuminate at step 160,indicating that the sensor system 24 may be disconnected from thepatient 16.

In embodiments that include period and/or frequency dials 56, 58, theamount of time prior to system lock is reduced through microprocessor54, which measures and records timing of the ON/OFF portions of theanalyzed signals and discards values that fall outside a predefinedtolerance of the expected period. Once a preset number of measuredpulses are acquired that fall within the predefined tolerance, locklight 64 illuminates.

After system lock, the DBS excitation pattern detected by sensor system24 may be converted to a timing signal 78 that includes a series oftiming pulses at step 162. This series of timing pulses simulates theenvelope of the cyclic DBS excitation signal based on the accumulateddata and predicts timing of the future DBS excitation signal generatedby pulse generator 20. In one embodiment, microprocessor 54 measures thefrequency and period corresponding to each ON/OFF pulse, discardsoutlying data, and generates a timing signal predictive of the DBSexcitation pattern from a subset of the accumulated data that fallwithin predefined tolerances. Each timing pulse of the timing signal hasa pulse width that approximates the pulse width of active or ON portionsof the cyclic DBS excitation pattern. The pulse width is determined bycalculating an average duration of the active portions of the DBSexcitation based on the recorded data.

After DBS waveform emulator 32 is locked on the waveform representingthe DBS excitation pattern of the patient 16, DBS waveform emulator 32may be configured to monitor the time-difference between the predictedand measured DBS stimulation state while the patient 16 remainsconnected to the sensor system 24. This assessment is carried bycomparing the timing of the pulse envelope converted from the real-timesignal output from sensor system 24 to the predicted timing of the pulseenvelope as determined based on the average of the data received fromthe sensor system 24 prior to system lock. The calculatedtime-difference between the predicted and measured DBS state (i.e.,wander) may be displayed on LCD display 70. Further, this wander or timeoffset may be calculated at various points during an MRI examination byreconnecting the patient 16 to the sensor system 24 in order to accessthe accuracy of the synchronization of the image acquisition timing. Atany point during or after the signal conversion, the output signal orwaveform corresponding to each of these steps may be displayed to anoperator such as on display 70 (FIG. 1) and/or stored within a database76. Exemplary waveforms corresponding to the various stages of the DBSsignal transformation are illustrated in FIG. 5. It will be understoodthat these waveforms are provided for explanatory purposes only andwould vary based on the particulars of the given DBS stimulation. Trace164 represents the raw input signal received by DBS waveform emulator 32during a given DBS. In addition to signals corresponding to the DBS, theraw trace 164 includes heart signals and may include transients at thestart of pulse generator 20. The central trace 166 represents the signalafter passing through the high pass filter 44, which removes theelectrical response from cardiac activity. After passing throughDC-blocking capacitor 50, comparator circuit 46, and pulse stretcher 52,the high-pass filtered signal is converted into a series of individualdigital logic pulses 168 that replicate the excitation timing 169 of theimplanted electrodes 12, as illustrated by trace 170. The final trace172 represents the output timing signal 78 used to trigger fMRI imageacquisition, which replicates the envelope 174 of the cyclic ON/OFFexcitation pattern of the DBS and includes a series of timing pulsesthat have a pulse width 176 that approximates the average duration of anON portion of the excitation pattern and represents the starting timeand stopping time of the ON portion, which are used to synchronize MRIimage acquisition.

Referring again to FIG. 4, after locking onto the cyclic stimulationpattern generated by the internal pulse generator 20, the bioelectricalsensors 26 are optionally disconnected from the patient 16 at step 178.The patient 16 enters the MRI scanner 86 free of any components ofsensor system 24 and the TTL timing signal predictive of the DBSwaveform continues to be output by microprocessor 54 based upon anaverage of the data acquired from sensor system 24 prior todisconnection. Alternatively, the patient 16 may enter the MRI scanner86 with the sensor system 24 still connected to the patient 16. In suchan embodiment, sensor system 24 is constructed of components that arecompatible with the imaging system such that the sensor system 24 mayremain affixed to the patient 16 during image acquisition. According toone embodiment, microprocessor 54 continues to receive and process datafrom sensor system 24 after the patient 16 enters the MM scanner 86until just prior to image acquisition, at which point the sensor system24 is turned off Alternatively, sensor system 24 may be configured tocontinue to acquire data during image acquisition. In such embodiments,DBS waveform emulator 32 may be configured with an additional filter(not shown) designed to filter out imaging gradients in the signalsreceived from sensor system 24.

At step 180 fMRI acquisition is configured with a periodicity equal tothe DBS periodicity measured by DBS waveform emulator 32. Once the fMRIsequence is armed, the first trigger provided by the DBS waveformemulator 32 indicating the predicted start of an ON portion of the DSexcitation will trigger the fMRI scan. The acquired image data issynchronized with the DBS excitation pattern, allowing data acquiredduring the stimulus (ON period) to be compared with data acquired duringthe OFF period to assess the neurological impact of the DBS.

After identifying a system lock at step 160, technique 146 mayalternatively generate a time stamp log at step 163, which may be laterused to bin medical images acquired during a DBS. In such an embodiment,the DBS waveform emulator 32 records the timing of the ON and OFFperiods of the DBS based on a reference time output by the clock 55provided within the DBS waveform emulator 32. The series of digitallogic pulses is then used to predict the future timing pattern of theexcitation signal. A time stamp log is generated from the predictedfuture timing pattern and is synchronized with the reference time outputof the clock 55. The predicted future timing pattern is determined in asimilar manner as the timing pulses described with respect to step 162based on calculated average durations of the active (ON) periods of theDBS excitation as determined from the acquired DBS signal. Each timestamp of the time stamp log reflects the predicted start time of futureactive transmission periods or ON periods of the cyclic DBS excitation.The time stamp log may additionally include predicted start times of thefuture non-active (OFF) periods and/or information regarding thepredicted pulse width or envelope of the ON periods.

The patient is disconnected from the sensor system at step 165 andmedical data is acquired from the patient thereafter. The medical datais acquired during the cyclic DBS excitation and is time stamped forlater analysis. According to various embodiments, the medical data mayinclude image data that is later reconstructed into MRI images, fMRIimages, PET images, or optical images, or data acquired from non-imagingmodalities such as, for example, EEG or MEG. However, one skilled in theart will recognize that the techniques described herein may be extendedfor use any type of medical data that might yield data reflective of theanatomical or functional response of a DBS system. The time-stampedmedical data (or the images reconstructed therefrom) is later accessedat step 167 and correlated with the DBS time stamp log at step 169.During this binning step, the DBS time stamp log is used to identify themedical data or images acquired during active periods and non-activeperiods of neurological excitation based on a correlation with the timestamps of the medical data.

Accordingly, embodiments of the present invention beneficially providean apparatus and method that is independent from the DBS programmer andthat identifies the excitation pattern of the DBS signal based onbioelectrical signals produced within the patient during a DBSexcitation. The disclosed apparatus and method process the detectedbioelectrical signals into a series of digital logic pulses that areused to emulate the DBS waveform. According to various embodiments, thisemulated DBS waveform may be used to predict the future timing sequenceof the DBS excitation after the sensor system is disconnected from thepatient or in the presence of interference generated by an imagingdevice such as an MRI scanner. The predicted timing sequence of the DBSexcitation may then be used to directly trigger image data acquisitionsynchronized to ON or active periods of the DBS excitation or be used togenerate a time stamp log that may be used to correlate medical data toON and OFF periods of the DBS excitation. The emulated DBS waveform mayfurther be used to assess the health of the DBS system, by permitting anoperator to determine whether the timing sequence of the DBS excitationis being carried out in accordance with the DBS programming.

A technical contribution for the disclosed method and apparatus is thatit provides for a computer implemented system and method for detectingthe excitation pattern of a DBS and converting the detected excitationpattern into a timing pulse that permits image data acquisition to besynchronized with the DBS. The disclosed method and apparatus furtherprovides for a computer implemented system and method for predicting afuture timing pattern of a DBS excitation signal and generating a timestamp log predictive of future active transmission periods ofneurological excitation therefrom.

One skilled in the art will appreciate that embodiments of the inventionmay be interfaced to and controlled by a computer readable storagemedium having stored thereon a computer program. The computer readablestorage medium includes a plurality of components such as one or more ofelectronic components, hardware components, and/or computer softwarecomponents. These components may include one or more computer readablestorage media that generally stores instructions such as software,firmware and/or assembly language for performing one or more portions ofone or more implementations or embodiments of a sequence. These computerreadable storage media are generally non-transitory and/or tangible.Examples of such a computer readable storage medium include a recordabledata storage medium of a computer and/or storage device. The computerreadable storage media may employ, for example, one or more of amagnetic, electrical, optical, biological, and/or atomic data storagemedium. Further, such media may take the form of, for example, floppydisks, magnetic tapes, CD-ROMs, DVD-ROMs, hard disk drives, and/orelectronic memory. Other forms of non-transitory and/or tangiblecomputer readable storage media not list may be employed withembodiments of the invention.

A number of such components can be combined or divided in animplementation of a system. Further, such components may include a setand/or series of computer instructions written in or implemented withany of a number of programming languages, as will be appreciated bythose skilled in the art. In addition, other forms of computer readablemedia such as a carrier wave may be employed to embody a computer datasignal representing a sequence of instructions that when executed by oneor more computers causes the one or more computers to perform one ormore portions of one or more implementations or embodiments of asequence.

Therefore, according to one embodiment of the invention, an apparatusfor analyzing bioelectrical signals generated during a deep brainstimulation (DBS) includes a housing having a signal input and a signaloutput and an electrical circuit disposed within the housing andelectrically coupled between the signal input and the signal output. Theelectrical circuit is configured to receive bioelectrical signalscorresponding to a cyclic excitation signal transmitted by a pulsegenerator during a DBS and generate an output signal comprising a seriesof timing pulses, wherein each timing pulse simulates an envelope of thecyclic excitation signal.

According to another embodiment of the invention, a method for analyzingbioelectrical signals generated during a deep brain stimulation (DBS)includes obtaining bioelectrical signals generated from excitationsignals transmitted by a pulse generator during a DBS. The method alsoincludes transforming the bioelectrical signals into a series of digitallogic pulses representing a plurality of active portions of the DBS,each active portion comprising a plurality of digital logic pulses. Themethod further includes generating a series of timing pulses from theseries of digital logic pulses, each timing pulse synchronized withpredicted timing of an active portion of the DBS.

According to yet another embodiment of the invention, a medical imagingsystem includes an imaging device configured to acquire medical imagedata from a patient and reconstruct medical images therefrom. Themedical imaging system also includes a sensor system configured todetect bioelectrical signals generated within the patient during a deepbrain stimulation (DBS) and a DBS signal emulator removeably coupleableto a trigger input of the imaging device and to the sensor system. TheDBS signal emulator is programmed to transform bioelectrical signalsreceived from the sensor system into a series of timing pulses havingpulse widths predictive of active periods of the DBS and output theseries of timing pulses to the trigger input of the imaging device.

This written description uses examples to disclose the invention,including the best mode, and also to enable any person skilled in theart to practice the invention, including making and using any devices orsystems and performing any incorporated methods. The patentable scope ofthe invention is defined by the claims, and may include other examplesthat occur to those skilled in the art. Such other examples are intendedto be within the scope of the claims if they have structural elementsthat do not differ from the literal language of the claims, or if theyinclude equivalent structural elements with insubstantial differencesfrom the literal languages of the claims.

What is claimed is:
 1. An apparatus for analyzing bioelectrical signalsgenerated during a deep brain stimulation (DBS), the apparatuscomprising: a housing having a signal input and a signal output; and anelectrical circuit disposed within the housing and electrically coupledbetween the signal input and the signal output, the electrical circuitconfigured to: receive bioelectrical signals corresponding to a cyclicexcitation signal transmitted by a pulse generator during a DBS; andgenerate an output signal comprising a series of timing pulses, whereineach timing pulse simulates an envelope of the cyclic excitation signal.2. The apparatus of claim 1 wherein the electrical circuit is furtherconfigured to: transform the bioelectrical signals into a series ofdigital logic pulses representing a plurality of active portions of thecyclic excitation signal, each active portion comprising a plurality ofdigital logic pulses; and wherein the electrical circuit furthercomprises a processor programmed to define each timing pulse having apulse width that approximates a duration of an active portion of theDBS.
 3. The apparatus of claim 2 wherein the processor is furtherprogrammed to: record timing of the series of digital logic pulses inreal time; calculate an average duration of the plurality of activeportions of the DBS based on the recorded timing; and define the pulsewidth of the timing pulse based on the calculated average duration. 4.The apparatus of claim 3 wherein the processor is further programmed to:count the number of recorded digital logic pulses; identify a signallock if the number of recorded digital logic pulses is within apredetermined threshold; and generate the output signal afteridentifying the signal lock.
 5. The apparatus of claim 3 wherein theprocessor is further programmed to: compare timing of the series ofdigital logic pulses to the series of timing pulses generated outputsignal; and calculate a timing offset based on the comparison, thetiming offset representing a difference between actual and predictedtiming of the cyclic excitation signal.
 6. The apparatus of claim 1wherein the electrical circuit is configured to transform thebioelectrical signals into a series of transistor-transistor logic (TTL)pulses.
 7. The apparatus of claim 1 wherein the electrical circuitcomprises: a comparator circuit that converts the bioelectrical signalsinto TTL pulses; and a pulse stretcher that correlates each TTL pulsewith a corresponding excitation signal generated during the DBS.
 8. Theapparatus of claim 1 wherein the signal output of the housing iselectrically coupleable to an auxiliary trigger input of an MRI system.9. The apparatus of claim 1 further comprising at least one sensorcoupled to the sensor input of the housing and coupleable to a patientto receive bioelectrical signals therefrom during a DBS.
 10. Theapparatus of claim 1 further comprising an adjustment device positionedon an external surface of the housing and coupled to the electricalcircuit, the adjustment device configured to modify a frequencythreshold of the received bioelectrical signals.
 11. A method foranalyzing bioelectrical signals generated during a deep brainstimulation (DBS), the method comprising: obtaining bioelectricalsignals generated from excitation signals transmitted by a pulsegenerator during a DBS; transforming the bioelectrical signals into aseries of digital logic pulses representing a plurality of activeportions of the DBS, each active portion comprising a plurality ofdigital logic pulses; and generating a series of timing pulses from theseries of digital logic pulses, each timing pulse synchronized withpredicted timing of an active portion of the DBS.
 12. The method ofclaim 11 further comprising generating the series of timing pulses suchthat each timing pulse represents a plurality of digital logic pulsescorresponding to a respective active portion of the DBS.
 13. The methodof claim 11 further comprising: recording timing of the series ofdigital logic pulses in real time; calculating an average duration ofthe plurality of active portions of the DBS based on the recordedtiming; and defining a pulse width of the series of timing pulses basedon the calculated average duration.
 14. The method of claim 11 furthercomprising: outputting the series of timing pulses to a medical imagingdevice; and triggering image data acquisition with the series of timingpulses.
 15. The method of claim 11 further comprising: transforming thebioelectrical signals into a series of transistor-transistor (TTL)pulses; and triggering fMRI image acquisition with the TTL pulses. 16.The method of claim 11 further comprising generating the series oftiming pulses such that each timing pulse has a pulse widthcorresponding to a duration of an active portion of the plurality ofactive portions of the DBS.
 17. A medical imaging system comprising: animaging device configured to acquire medical image data from a patientand reconstruct medical images therefrom; a sensor system configured todetect bioelectrical signals generated within the patient during a deepbrain stimulation (DBS); and a DBS signal emulator removeably coupleableto a trigger input of the imaging device and to the sensor system, theDBS signal emulator programmed to: transform bioelectrical signalsreceived from the sensor system into a series of timing pulses havingpulse widths predictive of active periods of the DBS; and output theseries of timing pulses to the trigger input of the imaging device. 18.The medical imaging system of claim 17 wherein the DBS signal emulatorcomprises an electrical circuit disposed within a housing; and whereinthe electrical circuit comprises: circuitry configured to transform thebioelectrical signals into a series of digital logic pulses; and aprocessor programmed to generate the series of timing pulses from theseries of digital logic pulses, each timing pulse having a pulse widththat simulates an envelope of a cyclic DBS excitation.
 19. The medicalimaging system of claim 18 wherein the processor is further programmedto: record timing of the series of digital logic pulses in real time;count the recorded series of digital logic pulses; and output a signallock indicator if the count exceeds a predefined threshold.
 20. Themedical imaging system of claim 17 wherein the imaging device comprisesa magnetic resonance imaging (MRI) device; and wherein the series ofpulses trigger MRI image acquisition.